The prevalence of antibiotic resistances in bacteria is becoming one of the leading public health threats. Current antibiotics interfere with the critical biological processes of the pathogens and cause death or growth arrest of the bacteria. As a result, antibiotic therapy exerts a strong selective pressure to favor emergence of antibiotic resistant strains. In order to circumvent this serious problem, alternative antimicrobial reagents are needed that suppress the virulence of the pathogens without generating strong selection for antibiotic resistance.
Group A streptococcus is among the most common human pathogens. Group A streptococci (GAS), also known as Streptococcus pyogenes, causes a variety of pathologies in different systems. From 5-15% of normal individuals are estimated to harbor this bacterium without sign of disease. GAS is highly specific to its human host and rarely infects other species. Infections caused by GAS include both mild conditions, such as tonsillitis, scarlet fever and impetigo, as well as life threatening diseases, such as toxic-shock-like syndrome and necrotizing fasciitis (Bisno et al., N. Engl. J. Med. 1996; 334:240-245). Strep throat accounts for 5-10% of sore throat cases. Ten million cases of mild GAS infection, such as strep throat and impetigo, occur in the United States every year. If left untreated, strep throat can lead to rheumatic fever and rheumatic heart disease, causing at least 15.6 million cases and 282,000 new cases respectively and resulting in 233,000 deaths each year Worldwide (Carapetis et al., Lancet Infect. Dis. 2005; 5:685-694). Even though treatment with antibiotics has greatly reduced mortality in the developed world, according to American Heart Association statistics, rheumatic fever and rheumatic heart disease still accounted for 3,248 deaths in the US in 2004. Furthermore, emergence of epidemic invasive GAS diseases poses another critical medical challenge given that little is known about the mechanism of invasiveness (Bisno et al., supra; Efstratiou et al., J. Antimicrob. Chemother. 2000; 45 Suppl:3-12; Stevens, Clin. Infect. Dis. 1992; 14:2-11).
Additional therapies for GAS infection, an important public health problem given the alarming emergence of antibiotic resistance among nearly all major human pathogens, are needed.